2-iodo-3-keto-Δ4 steroids, process for their production, as well as their further processing

Abstract

The new intermediate products of general formula I ##STR1## in which R 1 stands for a hydrogen atom or a straight-chain or branched alkyl group with 1 to 4 carbon atoms, R 2 stands for a hydrogen atom or a methyl group, R 3 stands for a hydrogen atom, R 4 stands for an acyloxy group with 1 to 4 carbon atoms in the acyl radical or R 3 and R 4 together stand for a keto-oxygen atom, are suitable in an excellent way for introducing a Δ 1 double bond in the steroid skelton with the simultaneous presence of a Δ 4 double bond, as well as a saturated carbonyl group, by clevage of hydrogen iodide with a base in an amidic solvent at elevated temperature. If R 2 stands for a hydrogen atom, the A-ring is aromatized after the hydrogen iodide cleavage. For the production of a new intermediate products, special iodization processes, which partially also allow a stereoselective control of the iodization, are used.

We claim: 
     
       1. A process for introducing a Δ 1  double bond in a steroid skeleton compound simultaneously having a Δ 4  double bond and at least one saturated carbonyl group, wherein a compound of formula I ##STR12## in which R 1  stands for a hydrogen atom or a straight-chain or branched alkyl group with 1 to 4 carbon atoms, R 2  stands for a hydrogen atom or a methyl group,   R 3  stands for a hydrogen atom,   R 4  stands for an acyloxy group with 1 to 4 carbon atoms in the acyl radical or   R 3  and R 4  together stand for a keto-oxygen atom, is dehydrohalogenated with a base in an amidic solvent at elevated temperature.   
     
     
       2. The process of claim 1, wherein the compound of formula I is dehydrohalogenated with magnesium oxide, lithium, sodium or potassium carbonate as the base. 
     
     
       3. The process of claim 1, wherein the compound of formula I is dehydrohalogenated in dimethylformamide or N-methyl-pyrrolidone as the solvent. 
     
     
       4. The process of claim 1, wherein the compound of formula I is dehydrohalogenated at a temperature of 100° to 150° C. 
     
     
       5. The process of claim 1, wherein 2α- or 2β-iodo-1α-methyl-androst-4-ene-3,17dione or a mixture of these isomers is dehydrohalogenated to Atamestan (1-methylandrosta-1,4-diene-3,17-dione). 
     
     
       6. The process of claim 1, wherein 2-iodo-19-norandrost-4-ene-3,17-dione is dehydrohalogenated to estrone (1,3,5-estratrien-3-ol-17-one). 
     
     
       7. The process of claim 1, wherein the dehydrohalogenation results in a compound of formula II ##STR13## in which R 1 , R 2 , R 3  and R 4  have the meaning indicated in formula I. 
     
     
       8. The process of claim 7, wherein R 2  stands for a hydrogen atom, and, after the dehydrohalogenation, the A-ring of the compound aromatizes with the formation of a compound of formula II' ##STR14## in which R 1 , R 3  and R 4  have he meaning as indicated in formula I. 
     
     
       9. The process of claim 1, wherein the dehydrohalogenation produces a product containing less than 1% of the by-product having double bond in the Δ 4  and Δ 6  positions.